A significant body of research has led to the current model of immunity and inflammation, as well as the dysregulation in immune and inflammatory disorders. It is currently understood that CD4+ helper T (TH) cells play a crucial role in host defense against various pathogens by orchestrating adaptive and innate immune responses. Upon T-cell receptor (TCR) activation by cognate antigen, naïve CD4+ T cells are committed to differentiate into at least five major subsets: TH1, TH2, TH17, iTreg and TFH, which are modulated by cytokine milieus. TH1 and TH17 cells are known to be the primary effectors of inflammation. However, the pathogenic roles of either TH1 or TH17 in various inflammatory disorders remain unclear. For example, recent studies conflict with previously understood paradigm of TH17 in multiple sclerosis (MS) pathogenicity (Haak et al., 2009), making it more challenging to identify potential drug targets for MS therapy. Similarly, while rheumatoid arthritis (RA) is traditionally understood to be a disorder mediated by tumor necrosis factor α (TNF-α), up to 40% of RA patients fail to respond to anti-TNF-α treatment.
Accordingly, there remains a significant unmet need for effective treatment methods for autoimmune and inflammatory disorders such as, e.g., MS and RA.